Assembly, Context and Innate add to ever-growing pile of dumped pipeline prospects

Biotech’s back burner is getting even busier. The latest set of earnings reports brought news of more drug programs that are being stopped or deprioritized, with Assembly Biosciences, Context Therapeutics and Innate Pharma all rethinking where to allocate their R&D budgets.

Antiviral startup Assembly paused development of one of its hepatitis B virus core inhibitors, ABI-H3733, after going over the early-phase data on it and another similar molecule. The biotech narrowed its focus based on phase 1 data on both candidates and a chronic toxicology observation for ABI-H3733. In the 26-week nonclinical toxicology study, Assembly saw “a time-dependent toxicity in one species.”

The toxicity was not seen in an earlier 28-day nonclinical study and may be a surmountable problem. But given the expectation that an additional chronic toxicology study in another species would be needed to take ABI-H3733 into phase 2, the biotech has paused work rather than incur the extra costs. 

Assembly ended 2022 with $91.6 million in the bank, a sum it forecasts will keep it going into the middle of next year. The biotech plans to report additional phase 1a data on its other core inhibitor, ABI-4334, next month and complete a filing to run a clinical trial of another asset, herpesvirus candidate ABI-5366, in the first half of next year.

The R&D rethink at Context was triggered by new data too. In an ongoing phase 2 trial of onapristone extended release in endometrial cancer, elevated liver function tests were seen in three patients, one of whom discontinued treatment. 

None of the liver test results were classed as serious adverse events but the biotech concluded that the need to analyze and mitigate future abnormalities will cause “significant incremental program costs and delays.” With $35.5 million to its name, Context isn’t in a position to weather such costs and delays. The biotech will now focus on a CLDN6 bispecific antibody, for which a clinical trial filing is planned for early next year.

Finally, Innate is stopping the development of anti-C5aR1 antibody avdoralimab in the rare skin condition bullous pemphigoid. The French drug developer took the candidate into the clinic as a solid tumor drug in 2018, working with AstraZeneca to test it in combination with a checkpoint inhibitor, but stopped the trial early. An attempt to reposition the molecule as a treatment for COVID-19 ended in failure. 

Throughout the changes, investigators at French hospitals continued to study the candidate in bullous pemphigoid, attracted by evidence that the C5aR1 pathway is strongly involved in the disease. However, Innate has now called time on the program, revealing it is discontinuing development in the indication and evaluating out-licensing as a potential next step.